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  The transcription factor Uncx4.1 acts in a short window of midbrain dopaminergic neuron differentiation.

Rabe, T., Griesel, G., Blanke, S., Kispert, A., Leitges, M., van der Zwaag, B., et al. (2012). The transcription factor Uncx4.1 acts in a short window of midbrain dopaminergic neuron differentiation. Neural Development, 7: 39. doi:10.1186/1749-8104-7-39.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-000E-CA98-4 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-CEF2-1
Genre: Journal Article

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Rabe, T.1, Author              
Griesel, G.1, Author              
Blanke, S.1, Author              
Kispert, A., Author
Leitges, M., Author
van der Zwaag, B., Author
Burbach, J. P., Author
Varoqueaux, F., Author
Mansouri, A.1, Author              
Affiliations:
1Research Group of Molecular Cell Differentiation, MPI for biophysical chemistry, Max Planck Society, ou_578588              

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Free keywords: Uncx4.1, Midbrain, mDA neurons, Ngn2, Pax6, Differentiation, Expression
 Abstract: Background: The homeobox containing transcription factor Uncx4.1 is, amongst others, expressed in the mouse midbrain. The early expression of this transcription factor in the mouse, as well as in the chick midbrain, points to a conserved function of Uncx4.1, but so far a functional analysis in this brain territory is missing. The goal of the current study was to analyze in which midbrain neuronal subgroups Uncx4.1 is expressed and to examine whether this factor plays a role in the early development of these neuronal subgroups. Results: We have shown that Uncx4.1 is expressed in GABAergic, glutamatergic and dopaminergic neurons in the mouse midbrain. In midbrain dopaminergic (mDA) neurons Uncx4.1 expression is particularly high around E11.5 and strongly diminished already at E17.5. The analysis of knockout mice revealed that the loss of Uncx4.1 is accompanied with a 25% decrease in the population of mDA neurons, as marked by tyrosine hydroxylase (TH), dopamine transporter (DAT), Pitx3 and Ngn2. In contrast, the number of glutamatergic Pax6-positive cells was augmented, while the GABAergic neuron population appears not affected in Uncx4.1-deficient embryos. Conclusion: We conclude that Uncx4.1 is implicated in the development of mDA neurons where it displays a unique temporal expression profile in the early postmitotic stage. Our data indicate that the mechanism underlying the role of Uncx4.1 in mDA development is likely related to differentiation processes in postmitotic stages, and where Ngn2 is engaged. Moreover, Uncx4.1 might play an important role during glutamatergic neuronal differentiation in the mouse midbrain.

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Language(s): eng - English
 Dates: 2012-12-08
 Publication Status: Published online
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 Rev. Method: Peer
 Identifiers: DOI: 10.1186/1749-8104-7-39
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Title: Neural Development
Source Genre: Journal
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Pages: 16 Volume / Issue: 7 Sequence Number: 39 Start / End Page: - Identifier: -